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Minimizing Cancer Risk Using Molecular Techniques: a Review

Immunosciences Lab, Incorporated Beverly Hills, California, Department of Medicine, Drew University School of Medicine and Science Los Angeles, California

Mamdooh Ghoneum

Department of Otolaryngology Drew University of Medicine and Science Los Angeles, California

Paul Choppa

Immunosciences Lab, Incorporated Beverly Hills, California

This review article summarizes molecular markers that can signal enhanced risk of cancer and provide clinicians with these clues in order to attempt the use of natural and synthetic compounds to intervene in the early precancerous stages of carcinogenesis before invasive disease begins.

With an aim such as this in mind, we have begun to apply molecular techniques based on many research articles to look for biomarkers capable of signaling a greater risk of cancer. It is possible to attain relatively quick answers by monitoring selected signs and damage in the body which provide the environment for abnormal cell growth and differentiation. These molecular techniques aim to uncover critical precancerous events taking place inside the body and identify measurable biologic flags signaling their occurrence.

For years now, scientists have understood that the onset of cancer is a gradual, step wise process that may unfold over the course of decades, rather than a single, fixed event that can be dated in a pathologist's report. Carcinogenesis usually encompasses the prolonged accumulation of injuries at several different biological levels and includes both genetic and biochemical changes in cells. At each of these levels there is an opportunity for intervention—a chance to prevent, slow or even halt the gradual march of healthy cells toward malignancy.

It is estimated that 75% of cancers are induced by chemicals; thus, if exposure to chemicals is avoided, cancer can be prevented.

Also, depending on the individual's genetic background, the ability to metabolize chemicals is different among the population. This means that, "you and I can be exposed to exactly the same amount of a chemical, " yet our response will differ because we metabolize carcinogens differently due to different rates of deoxyribonucleic acid (DNA) repair, apoptosis, and mitosis or different levels of Phase I and Phase II detoxification enzymes. This, along with a more or less efficient immune system, may promote tumor formation or destroy a cancer cell at its earliest stage of development.

Therefore, measurement of the biologic markers such as DNA and protein adducts, DNA damage, programmed cell death, DNA repair system, mitosis, gene activation, levels of antioxidants and efficient immune function described in this chapter and summarized in Figures 2 and 10, are biological clues indicating that the body has been assaulted by toxic (or cancer-causing) agents. This early identification of biomarkers for special vulnerability to the effects of chemicals and detection of selected signs of precancerous damage in the body may culminate preventive measures and the saving of lives.

Key Words: 2. Abbreviations: AFB • aflatoxin B1 • AhR • Ah receptor • AIDS • acquired immune deficiency syndrome • ATP • adenosine triphosphate • BPDE • benzo(a)pyrene • CDKs • cyclin-dependent kinases • CFIDS • chronic fatigue immune dysfunction syndrome • CFS • chronic fatigue syndrome • CYP1A1 • cytochrome P450-1A1 • CYP2D6 • cytochrome P2D6 • F-dUTP • flourescent-tagged deoxyuridine triphosphate nucleotides • Gx • gap phase-x • GSTs • glutathione S-transferases • HIV • human immunodeficiency syndrome • M • mitosis phase • MPP+ • 1-methyl-4-phenylpyridinium ion • MPTP • 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine • NAT • N- Acetyltransferase • NF-kB • nuclear factor k B • NK • natural killer cell • PAH • polycyclic aromatic hydrocarbon • PBLs • peripheral blood lymphocytes • PCBs • coplanar biphenals • PCDDs • polychlorinated dibenzo-p-dioxins • PCDFs • dibenzofurans • PCR • polymerase chain reaction • PI • propidium iodide • PKC • protein kinase C • ppt • parts per trillion • pRB • powerful growth-inhibitory protein molecule • PS • phosphotidylserine • R • restriction point • RT • reverse transcription • RT-PCR • reverse transcriptase polymerase chain reaction • S • DNA synthesis phase • TCDD • tetra-chlorodibenzo-p-dioxin • TdT • deoxynucleotidyl transferase • tSBO • trans-stilbene oxide • WBCs • white blood cells.

Toxicology and Industrial Health, Vol. 13, No. 5, 589-626 (1997)
DOI: 10.1177/074823379701300503


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